The observation that inbred mice and rats can be immunized against their own tumors or tumors of the same genetic background have led to a hypothesis that tumor-specific antigens exist. In essence, these studies showed that mice vaccinated with inactivated cancer cells are immune to subsequent challenges of live cancer cells. The phenomenon was shown to be individually tumor-specific, in that mice were immune specifically to the tumors used to immunize them and not to other tumors. The demonstration of immunogenicity of cancer cells led to a search for the cancer-derived molecules which elicit resistance to tumor challenges. The general approach in these experiments was to fractionate cancer-derived proteins and test them individually for their ability to immunize mice against the cancers from which the fractions were prepared.
One of the major difficulties in cancer immunotherapy has been the possibility that similar to the situation among animal cancers, each human cancer is different from all other cancers, i.e., human cancers, like cancers of experimental animals, are antigenically distinct. Clearly, there is some recent evidence for existence of common human tumor antigens (Kawakami et al., 1991, Darrow et al., 1989), and this augurs well for prospects of cancer immunotherapy. Nonetheless, in light of the overwhelming evidence from experimental and human systems, it is reasonable to assume that at the very least, human tumors would show tremendous antigenic diversity and heterogeneity.
The prospect of identification of the immunogenic antigens of individual tumors from cancer patients (or even of `only` several different types of immunogenic antigens in case the antigens are shared), is daunting to the extent of being impractical. Numerous studies on vaccination against infectious diseases have shown that it is necessary to first identify and characterize the immunogenic antigens.
For the reasons described above, such a strategy is impractical for vaccination or other forms of immuno-therapy against human cancers. Thus, there is a need to develop alternate methods for obtaining antigenic preparations which do not require such daunting identification of specific antigens from tumors of individual patients and avoids the difficulties and hazards associated with attenuation and inactivation of viruses.